PMID- 31364139
OWN - NLM
STAT- MEDLINE
DCOM- 20200930
LR  - 20200930
IS  - 2284-0729 (Electronic)
IS  - 1128-3602 (Linking)
VI  - 23
IP  - 14
DP  - 2019 Jul
TI  - Simvastatin alleviates inflammation and oxidative stress in rats with cerebral 
      hemorrhage through Nrf2-ARE signaling pathway.
PG  - 6321-6329
LID - 18455 [pii]
LID - 10.26355/eurrev_201907_18455 [doi]
AB  - OBJECTIVE: To investigate the regulatory effects of simvastatin on the 
      inflammation and oxidative stress in rats with cerebral hemorrhage through the 
      nuclear factor E2-related factor 2-antioxidant response element (Nrf2-ARE) 
      signaling pathway. MATERIALS AND METHODS: A total of 120 healthy male rats 
      weighing 280-300 g and 7-8 weeks old were selected to establish the traumatic 
      brain injury (TBI) model. Rats were divided into group A (trauma operation, 
      n=30), group B (no treatment, n=30), group C (drug administration after trauma 
      operation, n=30), and group D (no trauma operation, drug administration, n=30). 
      Cerebral edema content in brain tissues was measured by calculating the dry and 
      wet weight. Neurological dysfunction was scored using the Garcia method. Positive 
      levels of the Toll-like receptor 4 (TLR4) and interleukin-1beta (IL-1beta) were 
      qualitatively analyzed via immunohistochemistry. Protein levels of TLR4 and IL-1beta 
      were quantitatively analyzed via Western blotting. Moreover, the brain injury 
      volume and neuronal apoptosis were evaluated via Nissl staining and terminal 
      deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining, 
      respectively. At 48 h after injury, activities of superoxide dismutase (SOD), 
      reduced glutathione (GSH), and oxidized glutathione (GSSG) in brain tissues were 
      detected, and levels of malondialdehyde (MDA) and nitric oxide (NO) were detected 
      using the enzyme activity assay kits. Finally, relative levels of the Nrf2-ARE 
      signaling pathway and its downstream molecules heme oxygenase-1 (HO-1) and NAD 
      (P)H dehydrogenase, quinone 1 (NQO1) were detected via reverse 
      Transcription-Polymerase Chain Reaction (RT-PCR) and Western blotting. RESULTS: 
      Compared with those in group B, cerebral edema content in brain tissues 
      significantly increased (p<0.05), the neurological dysfunction score 
      significantly declined (p<0.05), and protein levels of TLR4 and IL-1beta were 
      significantly upregulated in group A (p<0.05). In group C, relative levels of 
      TLR4 and IL-1beta were down-regulated, cerebral edema content decreased, and the 
      neurological dysfunction score significantly increased (p<0.05). After 48 h, 
      activities of SOD, reduced GSH and GSSG and levels of MDA and NO all increased, 
      and levels of MDA and NO declined in group C (p<0.05). Western blotting and 
      RT-PCR showed that simvastatin could increase the transcriptional level of Nrf2. 
      After simvastatin intervention, expression levels of downstream molecules HO-1 
      and NQO1 were upregulated. CONCLUSIONS: Simvastatin alleviates TLR4-mediated 
      inflammatory injury, promotes neurological recovery and resists oxidative stress 
      through the Nrf2-ARE signaling pathway, thus exerting a neuroprotective effect in 
      TBI.
FAU - Zhang, C-Y
AU  - Zhang CY
AD  - Department of Emergency, First Affiliated Hospital of Jiamusi University, 
      Jiamusi, China. 15694548231@163.com.
FAU - Ren, X-M
AU  - Ren XM
FAU - Li, H-B
AU  - Li HB
FAU - Wei, W
AU  - Wei W
FAU - Wang, K-X
AU  - Wang KX
FAU - Li, Y-M
AU  - Li YM
FAU - Hu, J-L
AU  - Hu JL
FAU - Li, X
AU  - Li X
LA  - eng
PT  - Journal Article
PL  - Italy
TA  - Eur Rev Med Pharmacol Sci
JT  - European review for medical and pharmacological sciences
JID - 9717360
RN  - 0 (IL1B protein, rat)
RN  - 0 (Interleukin-1beta)
RN  - 0 (NF-E2-Related Factor 2)
RN  - 0 (Nfe2l2 protein, rat)
RN  - 0 (Tlr4 protein, rat)
RN  - 0 (Toll-Like Receptor 4)
RN  - AGG2FN16EV (Simvastatin)
SB  - IM
MH  - Animals
MH  - Antioxidant Response Elements
MH  - Cerebral Hemorrhage/*drug therapy/immunology
MH  - Disease Models, Animal
MH  - Down-Regulation
MH  - Gene Expression Regulation/drug effects
MH  - Interleukin-1beta/metabolism
MH  - Male
MH  - NF-E2-Related Factor 2/*genetics
MH  - Oxidative Stress/*drug effects
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Signal Transduction/drug effects
MH  - Simvastatin/*administration & dosage/pharmacology
MH  - Toll-Like Receptor 4/metabolism
EDAT- 2019/08/01 06:00
MHDA- 2020/10/02 06:00
CRDT- 2019/08/01 06:00
PHST- 2019/08/01 06:00 [entrez]
PHST- 2019/08/01 06:00 [pubmed]
PHST- 2020/10/02 06:00 [medline]
AID - 18455 [pii]
AID - 10.26355/eurrev_201907_18455 [doi]
PST - ppublish
SO  - Eur Rev Med Pharmacol Sci. 2019 Jul;23(14):6321-6329. doi: 
      10.26355/eurrev_201907_18455.